In humans and animals, low-moderate doses of amphetamine have been reported to increase physical performance and endurance, while toxic doses produce muscle weakness and paralysis. While enhancement in such physical activities has been generally attributed to the central stimulating effects of amphetamine, these studies seek to determine whether such effects may also be attributed to drug enhancement or impairment of neuromuscular transmission, respectively. We have observed that low concentrations of amphetamine enhance the amplitude of muscle contractions of the isolated phrenic nerve-diaphragm, while high concentrations produce neuromuscular blockade. Our results suggest that this drug blocks neuromuscular transmission with characteristics that resemble the nondepolarizing blockade associated with curare-like drugs. In other studies, we have observed that low doses of amphetamine enhance the treadmill performance of rats, in vivo, while high doses produce muscle blockade and a decrement in performance. BIBLIOGRAPHIC REFERENCES: Amphetamine inhibition of alpha-bungarotoxin binding to mouse hemidiaphragms. K.A. Skau and M.C. Gerald, Fed. Proc. 36: 977, 1977. Catecholaminergic involvement in the effects of amphetamine isomers on seizure susceptibility. M.C. Gerald and T.K. Gupta, Eur. J. Pharmacol. 41: 231-234, 1977.